CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

491 SIMILAR EFFICACY & SAFETY BY SUBGROUP IN DRIVE-AHEAD: DOR/3TC/ TDF VERSUS EFV/FTC/TDF Chloe Orkin 1 , Kathleen E. Squires 2 , Jean-Michel Molina 3 , Paul E. Sax 4 , Wing-Wai Wong 5 , Otto Sussmann 6 , Richard Kaplan 7 , Anthony Rodgers 8 , Xia Xu 8 , Gina Lin 8 , Sushma Kumar 8 , George G. Hanna 8 , Carey Hwang 8 , Elizabeth Martin 8 1 Royal London Hospital, London, UK, 2 Thomas Jefferson University, Philadelphia, PA, USA, 3 University Paris Diderot, Paris, France, 4 Brigham and Women’s Hospital, Boston, MA, USA, 5 Taipei Medical University, Taipei, Taiwan, 6 Asistencia Cientifica de Alta Complejidad SAS, Bogota, Columbia, 7 Desmond Tutu HIV Foundation, Cape Town, South Africa, 8 Merck & Co, Inc, Kenilworth, NJ, USA Background: In the phase 3 DRIVE-AHEAD trial, a once-daily single-tablet regimen of doravirine 100 mg, lamivudine 300 mg, and tenofovir DF 300 mg (DOR/3TC/TDF) demonstrated non-inferior efficacy and a superior safety profile for neuropsychiatric events and fasting lipids compared to efavirenz 600 mg, emtricitabine 200 mg, and tenofovir DF 300 mg (EFV/FTC/TDF) at Week 48. To further characterize the effects of DOR/3TC/TDF, Week 48 results were examined by pre-specified subgroups (efficacy) and selected prognostic subgroups (safety). Methods: DRIVE-AHEAD is a randomized (1:1), multicenter, double-blind, 96-week non-inferiority trial of DOR/3TC/TDF vs EFV/FTC/TDF in HIV-1 infected treatment-naïve adults. Randomization was stratified by screening HIV-1 RNA (≤/>100,000 copies/mL) and hepatitis B/C co-infection (yes/no). The primary endpoint was the proportion of participants achieving HIV-1 RNA <50 copies/ mL at Week 48 (FDA Snapshot approach). For the current analysis, Week 48 efficacy results were summarized within pre-specified subgroups using the Observed Failure approach (participants with data missing for reasons other than lack of efficacy were excluded). Adverse events were also summarized by selected subgroups (gender, race/ethnicity, hepatitis co-infection, and baseline CD4+ T-cell count). Results: Baseline characteristics were balanced across the treatment groups. In the primary analysis, HIV-1 RNA <50 copies/mL was achieved by 84% of DOR/3TC/TDF recipients and 81% of EFV/FTC/TDF recipients at Week 48 (difference 3.5%, 95% CI [-2.0, 9.0]). Of the 728 participants who received study drug (364 in each treatment group), 677 (93%) were included in the subgroup efficacy analyses. Across the prespecified and selected demographic and baseline prognostic factors, the proportions of participants with HIV-1 RNA <50 copies/mL at Week 48 were comparable between the treatment regimens (table). Similar results were observed using the HIV-1 RNA cutoffs of 40 and 200 copies/mL and in the change from baseline in CD4+ T-cell counts. In the safety analysis, similar adverse event rates between treatment groups were observed across the subgroups. Conclusion: At Week 48, across all baseline subgroups and prognostic factors, DOR/3TC/TDF demonstrated virologic and immunologic efficacy and safety comparable to that of EFV/FTC/TDF in HIV-1 treatment-naïve adults.

Poster Abstracts

492 AGE, GENDER, AND RACE ANALYSES OF D/C/F/TAF IN HIV-1 TREATMENT NAÏVE PATIENTS Bruce Rashbaum 1 , Cheryl McDonald 2 , Cristina Mussini 3 , Christoph D. Spinner 4 , John Jezorwski 5 , Eric Y. Wong 6 , Kimberley Brown 6 1 Capital Medical Associates, Washington, DC, USA, 2 Tarrant County Infectious Disease Associates, Fort Worth, TX, USA, 3 University of Modena and Reggio Emilia, Modena, Italy, 4 Technical University of Munich, Munich, Germany, 5 Janssen Research & Development, Pennington, NJ, USA, 6 Janssen Scientific Affairs, LLC, Titusville, NJ, USA Background: Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the only single-tablet regimen in development for HIV-1 infection that contains darunavir and F/TAF. AMBER evaluated the efficacy and safety of D/C/F/TAF 800/150/200/10 mg versus control (D/C+F/tenofovir disoproxil fumarate [TDF]) in antiretroviral treatment (ART)-naïve, HIV-1–infected adults. We present Week 48 results based on age, gender, and race. Methods: In AMBER, a phase 3, randomized (1:1), non-inferiority trial, the primary endpoint was proportion of patients with virologic response (viral load [VL] <50 copies[c]/mL; FDA snapshot) at Week 48. Patients with baseline resistance-associated mutations to agents other than D, F, or TDF could be included. Safety was assessed by adverse event (AE) rates and changes in bone mineral density and eGFR from baseline to Week 48. Subgroups evaluated were: age ≤50 versus >50 y, men versus women, and non-black/African American (AA) versus black/AA race. Results: A total of 725 patients were randomized and treated; 68 (9.4%) were >50 y, 85 (11.7%) women, and 80 (11.5%) black/AA. Overall, virologic response rates were 91.4% for D/C/F/TAF and 88.4% for control (difference, 2.7%; 95% confidence interval, –1.6% to 7.1%); response rates with D/C/F/ TAF were similar to control across age, gender, and race subgroups (Table). In the total population, patients in the D/C/F/TAF and control arms had similar rates of discontinuation due to an AE (1.9% vs 4.4%, respectively), worst grade 3-4 AEs (5.2% vs 6.1%), and serious AEs (4.7% vs 5.8%). Similarly, there were no clinically relevant differences across subgroups; in general, there were numerically fewer AEs in the D/C/F/TAF arm versus control (Table). There were no deaths. Improvement in bone (bone loss/atrophy AEs, bone mineral density) and renal (eGFR) safety parameters were observed for D/C/F/TAF versus control across subgroups, consistent with results in the total population.

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